Spinal cord terminations of the medial wall motor areas in macaque monkeys

Abstract

We used anterograde transport of wheat germ agglutinin-horseradish peroxidase to examine the pattern of spinal termination of efferents from the supplementary motor area (SMA) and the two caudal cingulate motor areas (CMAd and CMAv). Our analysis was limited to cervical segments of the macaque. For comparison, we also examined the pattern of termination of efferents from the primary motor cortex (M1). The SMA, CMAd, CMAv, and M1 all terminate in the ventral horn (lamina IX). Thus, all of these motor areas appear to have direct connections with spinal motoneurons, particularly those innervating muscles of the fingers and wrist. All of the motor areas also terminate in the intermediate zone of the spinal cord (laminae V-VIII). Terminations from the SMA and M1 were densest in three regions: (1) dorsolaterally within laminae V-VII; (2) dorsomedially within lamina VI; and (3) ventromedially within lamina VII and adjacent lamina VIII. In contrast, efferents from the CMAd terminate most densely in the dorsolateral portion of the intermediate zone, whereas those from the CMAv were concentrated in the dorsomedial region. Thus, the CMAd and CMAv may innervate distinct sets of interneurons that project directly to motoneurons, and thereby influence specific aspects of segmental motor control. These results suggest that corticospinal projections from the SMA, CMAd, and CMAv are in many respects similar to those of efferents from M1. Consequently, each of the motor areas on the medial wall has the potential to generate and control movement at the level of the spinal cord and may provide an anatomical substrate for the recovery of motor function that follows damage to M1.

Fig. 1.

Origin of corticospinal projections from the motor areas on the medial wall of the hemisphere. This reconstruction of the frontal lobe of a macaque brain indicates the origin of corticospinal neurons (shaded regions) that project to the cervical segments of the spinal cord. In this view, the medial wall is unfolded and reflected upward to reveal the cingulate sulcus. The anterior bank of the central sulcus is also unfolded. A dashed linemarks the fundus of each unfolded sulcus. The centers of the different cortical motor areas are designated by the circled letters. The boundaries between the motor areas and cytoarchitectonic areas (identified by numbers) are denoted with dotted lines. Ar Genu (witharrow), Level of the genu of the arcuate sulcus;ArSi, inferior limb of the arcuate sulcus;ArSs, superior limb of the arcuate sulcus;CC, corpus callosum; CgG, cingulate gyrus; CgSd, dorsal bank of the cingulate sulcus;CgSv, ventral bank of the cingulate sulcus;CMAd, cingulate motor area on the dorsal bank of the cingulate sulcus; CMAr, rostral cingulate motor area;CMAv, cingulate motor area on the ventral bank of the cingulate sulcus; CS, central sulcus; M1, primary motor cortex; PMd, dorsal premotor area;PMv, ventral premotor area; PS, principal sulcus; SGm, medial portion of the superior frontal gyrus; SPcS, superior precentral sulcus;SMA, supplementary motor area. Adapted from Dum and Strick (1991b).

Fig. 2.

Location of cortical injection sites.A, Injection sites in the SMA (animal R3) and M1 (animal R4) are illustrated on a map of the frontal lobe. B, Injection site involving both the CMAd and the CMAv (animal R9). C, The injection sites in the CMAd (animal J6) and the CMAv (animal J7) are shown on a single map of the medial wall. The dense core of reaction product (shaded region) at each injection site was considered to be the site of uptake and anterograde transport. The dotted linesurrounding each dense core indicates the surrounding region with heavily labeled neurons and strong background labeling. Calibration inA applies to all maps. For conventions and abbreviations, see Figure 1.

Fig. 3.

Laminar organization of the cervical spinal cord. Photomicrograph of a coronal section of spinal segment T1 of a macaque stained with cresyl violet. Laminar borders adapted from the criteria of Rexed (1952) and Apkarian and Hodge (1989). c, Central; l, lateral; m, medial.

Fig. 4.

Corticospinal terminations in contralateral C7.A, Photomicrograph under dark-field/polarized light of TMB labeling after WGA-HRP injections into the SMA. SMA efferents terminate densely in four regions of the gray matter (numbered arrows; see Results for further description). B, TMB labeling after injections into M1. M1 efferents terminate densely in the same four regions of the gray matter, as do SMA efferents. Laminar borders are indicated as in Figure 3.

Fig. 5.

Corticospinal terminations in ipsilateral C7.A, TMB labeling after WGA-HRP injections into the SMA.B, TMB labeling after injections into M1. Laminar borders are indicated as in Figure 3.

Fig. 6.

SMA terminations in contralateral cervical segments of animal R3. Each figure shows a gradient density analysis of corticospinal terminations at one of four segmental levels in the cervical spinal cord. Digitally captured images of spinal cord terminations were color-coded: white = the most intense 10% of illuminated pixels, yellow = 60–90%, red = 30–60%, blue = the least intense 30%. The pattern of SMA terminations at each segmental level is similar and includes some terminations in dorsolateral lamina IX where motoneurons are located.

Fig. 7.

Quantitative analysis of corticospinal terminations. Top row, Histograms indicate the percentage of the total number of illuminated pixels that were found in each lamina. The percentage of total label in a lamina was calculated separately for each segment of the cervical enlargement (C5–T1) and then was averaged across segments to determine the values represented in a histogram. The histograms provide an indication of the overall distribution of terminations to each lamina from the SMA (animal R3), CMAd/CMAv (animals R9 and R10), and M1 (animal R4). Bottom row, Histograms indicate the percentage of area in each lamina that had illuminated pixels. These values are averages for all segments of the cervical enlargement. 9l, Lateral cell column of lamina IX; 9m, medial cell column of lamina IX.

Fig. 8.

Percentage of the illuminated pixels in the contralateral gray matter that are located in the lateral cell column of lamina IX. The CMAd/CMAv and SMAhistograms each represent the average of two animals.

Fig. 9.

CMAd/CMAv terminations in contralateral cervical segments of animal R9. These images are displayed using the same conventions as in Figure 6. The pattern of CMAd/CMAv terminations at each cervical level is similar to the SMA pattern (Fig. 6), except in medial lamina VIII.

Fig. 10.

CMAd and CMAv terminations in contralateral T1.A, TMB labeling after injections into the CMAd (animal J6). B, TMB labeling after injections into the CMAv (animal J7). These images are displayed using the same conventions as in Figure 6 except they are presented in gray scale.

Fig. 11.

M1 terminations in contralateral cervical segments of animal R4. These images are displayed using the same conventions as in Figure 6. The pattern of M1 terminations at each cervical level is similar to the SMA pattern (Fig. 6), even though the overall density of M1 terminations is higher.